Simple Summary
Soft tissue sarcomas (STS) are a broad group of aggressive connective tissue tumors that affect dogs and humans. This study aimed to compare STS between the two species and identify the shared characteristics of their immune contextures. We analyzed clinical data, tumor histopathology, and gene expression profiles from STS from 75 dogs, and compared them to human STS. Our results revealed that castrated male dogs had worse progression-free survival and shorter time to metastasis compared to spayed females, suggesting that factors other than sex hormones determine patients’ outcome. In addition, canine STS tumors exhibited immune contextures that mirrored those observed in human, characterized by significant infiltration of CD204 macrophages. In cases of increased FOXP3+ Tregs presence, a significant correlation with shorter progression-free intervals was observed. We also identified similarities in gene expression between canine STS and human undifferentiated pleomorphic sarcoma, with MYC dysregulation in canine indicating poor prognosis. The results of this study highlight the potential of canine STS as a preclinical model for the disease in humans and for advancing the development of novel immunotherapies.
Abstract
Background/Objectives: Soft tissue sarcomas (STS) remain a therapeutic challenge due to their limited response to radiation and conventional chemotherapies. While recent advances in immunotherapy have improved outcomes in several cancers, these strategies have been largely disappointing in STS patients. Naturally occurring STS in dogs have been suggested as a spontaneous, immunocompetent model of human STS, but further characterization of its tumor immune microenvironment is needed to validate its relevance. This study aimed to identify the shared immune-related components of canine and human STS and to determine how these factors influence the tumor biology, progression, and prognosis. Results: Data from 75 dogs with STS was analyzed. In addition, we characterized the tumor immune microenvironment using immunohistochemistry and compared gene expression between canine and human STS. Progression-free survival and time to metastasis was significantly longer in castrated males in comparison to females. In addition, dogs with appendicular tumors had better progression- and recurrence-free survival, whereas tumor recurrence following surgical excision was associated with a shorter time to metastasis. Immunohistochemistry revealed infiltration of CD204+ cells in most of the tumors examined, and disease-free intervals were shorter in dogs with tumors exhibiting FOXP3+ cell infiltration. Gene expression profiling demonstrated similarities between canine STS and human undifferentiated pleomorphic sarcomas, with MYC dysregulation emerging as a poor prognostic indicator for dogs. Conclusion: The comparative analysis between the human and canine STS microenvironment offers a valuable insight into the clinical behavior and immune landscape of canine STS, underscoring its potential as a relevant preclinical model for the translation and development of future immunotherapies.